The genomic landscapes of human breast and colorectal cancers

Laura D. Wood; D. Williams Parsons; Siân Jones; Jimmy Lin; Tobias Sjöblom; Rebecca J. Leary; Dong Shen; Simina M. Boca; Thomas Barber; Janine Ptak; Natalie Silliman; Steve Szabo; Zoltan Dezso; Vadim Ustyanksky; Tatiana Nikolskaya; Yuri Nikolsky; Rachel Karchin; Paul A. Wilson; Joshua S. Kaminker; Zemin Zhang; Randal Croshaw; Joseph Willis; Dawn Dawson; Michail Shipitsin; James K V Willson; Saraswati Sukumar; Kornelia Polyak; Ho Park Ben; Charit L. Pethiyagoda; P. V Krishna Pant; Dennis G. Ballinger; Andrew B. Sparks; James Hartigan; Douglas R. Smith; Erick Suh; Nickolas Papadopoulos; Phillip Buckhaults; Sanford D. Markowitz; Giovanni Parmigiani; Kenneth W. Kinzler; Victor E. Velculescu; Bert Vogelstein

doi:10.1126/science.1145720

The genomic landscapes of human breast and colorectal cancers

Laura D. Wood, D. Williams Parsons, Siân Jones, Jimmy Lin, Tobias Sjöblom, Rebecca J. Leary, Dong Shen, Simina M. Boca, Thomas Barber, Janine Ptak, Natalie Silliman, Steve Szabo, Zoltan Dezso, Vadim Ustyanksky, Tatiana Nikolskaya, Yuri Nikolsky, Rachel Karchin, Paul A. Wilson, Joshua S. Kaminker, Zemin ZhangRandal Croshaw, Joseph Willis, Dawn Dawson, Michail Shipitsin, James K V Willson, Saraswati Sukumar, Kornelia Polyak, Ho Park Ben, Charit L. Pethiyagoda, P. V Krishna Pant, Dennis G. Ballinger, Andrew B. Sparks, James Hartigan, Douglas R. Smith, Erick Suh, Nickolas Papadopoulos, Phillip Buckhaults, Sanford D. Markowitz, Giovanni Parmigiani, Kenneth W. Kinzler, Victor E. Velculescu, Bert Vogelstein

Simmons Comprehensive Cancer Center

Research output: Contribution to journal › Article › peer-review

2570 Scopus citations

Abstract

Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.

Original language	English (US)
Pages (from-to)	1108-1113
Number of pages	6
Journal	Science
Volume	318
Issue number	5853
DOIs	https://doi.org/10.1126/science.1145720
State	Published - Nov 16 2007

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Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjöblom, T., Leary, R. J., Shen, D., Boca, S. M., Barber, T., Ptak, J., Silliman, N., Szabo, S., Dezso, Z., Ustyanksky, V., Nikolskaya, T., Nikolsky, Y., Karchin, R., Wilson, P. A., Kaminker, J. S., ... Vogelstein, B. (2007). The genomic landscapes of human breast and colorectal cancers. Science, 318(5853), 1108-1113. https://doi.org/10.1126/science.1145720

Wood, LD, Parsons, DW, Jones, S, Lin, J, Sjöblom, T, Leary, RJ, Shen, D, Boca, SM, Barber, T, Ptak, J, Silliman, N, Szabo, S, Dezso, Z, Ustyanksky, V, Nikolskaya, T, Nikolsky, Y, Karchin, R, Wilson, PA, Kaminker, JS, Zhang, Z, Croshaw, R, Willis, J, Dawson, D, Shipitsin, M, Willson, JKV, Sukumar, S, Polyak, K, Ben, HP, Pethiyagoda, CL, Pant, PVK, Ballinger, DG, Sparks, AB, Hartigan, J, Smith, DR, Suh, E, Papadopoulos, N, Buckhaults, P, Markowitz, SD, Parmigiani, G, Kinzler, KW, Velculescu, VE & Vogelstein, B 2007, 'The genomic landscapes of human breast and colorectal cancers', Science, vol. 318, no. 5853, pp. 1108-1113. https://doi.org/10.1126/science.1145720

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abstract = "Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene {"}mountains{"} and a much larger number of gene {"}hills{"} that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.",

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AU - Jones, Siân

AU - Lin, Jimmy

AU - Sjöblom, Tobias

AU - Leary, Rebecca J.

AU - Shen, Dong

AU - Boca, Simina M.

AU - Barber, Thomas

AU - Ptak, Janine

AU - Silliman, Natalie

AU - Szabo, Steve

AU - Dezso, Zoltan

AU - Ustyanksky, Vadim

AU - Nikolskaya, Tatiana

AU - Nikolsky, Yuri

AU - Karchin, Rachel

AU - Wilson, Paul A.

AU - Kaminker, Joshua S.

AU - Zhang, Zemin

AU - Croshaw, Randal

AU - Willis, Joseph

AU - Dawson, Dawn

AU - Shipitsin, Michail

AU - Willson, James K V

AU - Sukumar, Saraswati

AU - Polyak, Kornelia

AU - Ben, Ho Park

AU - Pethiyagoda, Charit L.

AU - Pant, P. V Krishna

AU - Ballinger, Dennis G.

AU - Sparks, Andrew B.

AU - Hartigan, James

AU - Smith, Douglas R.

AU - Suh, Erick

AU - Papadopoulos, Nickolas

AU - Buckhaults, Phillip

AU - Markowitz, Sanford D.

AU - Parmigiani, Giovanni

AU - Kinzler, Kenneth W.

AU - Velculescu, Victor E.

AU - Vogelstein, Bert

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AB - Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.

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The genomic landscapes of human breast and colorectal cancers

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